Clinical and Translational Science
April 1, 2026
Matthijs W Van Hoogdalem, Dong-Jing Fu, Wayne C. Drevets et al.
Major depressive disorder (MDD) imposes a substantial burden worldwide, with treatment-resistant depression (TRD) and major depressive disorder with acute suicidal ideation or behavior (MDSI) representing two of the most severe clinical challenges. Conventional antidepressants often require several weeks to exert benefit, leaving patients symptomatic and at risk during this delay. Esketamine...
FOCUS: The Journal of Lifelong Learning in Psychiatry
April 1, 2026
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3...
JAMA Psychiatry
July 2, 2025
Adam Janik, Xin Qiu, Rosanne Lane et al.
40 citations
Esketamine nasal spray, administered in conjunction with an oral antidepressant, is approved for treatment-resistant depression (TRD). However, the efficacy of esketamine nasal spray administered as monotherapy for patients with TRD has not yet been evaluated. To assess the efficacy and safety of esketamine monotherapy compared to placebo in reducing depressive symptoms in patients with TRD....
The International Journal of Neuropsychopharmacology
June 6, 2025
Naim Zaki, Li Nancy Chen, Rosanne Lane et al.
32 citations
The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) vs non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months. To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD. Phase 3, open-label,...
Journal of the American Academy of Child & Adolescent Psychiatry
March 7, 2025
Colette Kosik-Gonzalez, Dong-Jing Fu, Li Nancy Chen et al.
14 citations
To evaluate the efficacy, safety, and tolerability of esketamine nasal spray vs psychoactive placebo (oral midazolam) in rapidly reducing depressive symptoms in adolescents with major depressive disorder at imminent risk for suicide. This double-blind, double-dummy, phase 2b study randomized (1:1:1:2) 147 adolescents (12 to <18 years old) to esketamine (28, 56, or 84 mg) or midazolam twice...
Quality of Life Research
November 2023
Carol Jamieson, Carla M. Canuso, Dawn F. Ionescu et al.
To assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI). Patient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18-64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the...
New England Journal of Medicine
October 4, 2023
Andreas Reif, Istvan Bitter, Jozefien Buyze et al.
197 citations
BACKGROUND: In treatment-resistant depression, commonly defined as a lack of response to two or more consecutive treatments during the current depressive episode, the percentage of patients with remission is low and the percentage with relapse is high. The efficacy and safety of esketamine nasal spray as compared with extended-release quetiapine augmentation therapy, both in combination with...
CNS Drugs
August 9, 2023
Meredith Castro, Samuel T. Wilkinson, Rayan K. Al Jurdi et al.
Background: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK...
Neuropsychopharmacology
May 12, 2023
Naim Zaki, Li Chen, Rosanne Lane et al.
122 citations
Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3...
Neuropsychiatric Disease and Treatment
March 31, 2023
Xu Chen, Xuan Hou, Daisy Bai et al.
Purpose: This Phase 3, multicenter study (NCT03434041) was conducted in primarily Chinese patients with treatment-resistant depression (TRD) to support the registration of esketamine nasal spray in China. Patients and methods: This randomized, double-blind, active-controlled study was conducted in China and the United States (US) in patients with TRD (single or recurrent episode). Eligible...
CNS Spectrums
July 29, 2022
Ibrahim Turkoz, Oliver Lopena, Giacomo Salvadore et al.
6 citations
Abstract Objective To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response. Methods A post hoc analysis of pooled data from ASPIRE I and ASPIRE II...
The International Journal of Neuropsychopharmacology
August 26, 2020
Dawn F. Ionescu, Dong-Jing Fu, Xin Qiu et al.
411 citations
BACKGROUND: Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment. METHODS: This double-blind study (ASPIRE II) randomized adults (aged 18-64 years) with MDD having active suicidal ideation with intent to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks, given with comprehensive standard of care (hospitalization ≥5...
The Journal of Clinical Psychiatry
May 11, 2020
Dong-Jing Fu, Dawn F. Ionescu, Xiang Li et al.
367 citations
OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of...